Pyridine → 2-(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-N-(5-dimethoxymethylpyrazin-2-yl)-propionamide

HRID 719885

반응식

HRID 719885 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[CH3:28][O:29][CH:30]([O:38][CH3:39])[C:31]1[N:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=1.N1C=CC=CC=1>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C)C=O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:37][C:34]2[CH:33]=[N:32][C:31]([CH:30]([O:38][CH3:39])[O:29][CH3:28])=[CH:36][N:35]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

참가 물질

8

반응물 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 218973555-Dimethoxymethyl-pyrazin-2-ylamine

생성물 1

HCID 104803762-(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-N-(5-dimethoxymethylpyrazin-2-yl)-propionamide수율 69.2%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 8028Tetrahydrofuran용매HCID 21877217Toluene methylene chloride용매

반응 조건

온도
25 °C

실험 절차

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 883 mg, 2.67 mmol) and oxalyl chloride (677 mg, 5.34 mmol) in methylene chloride/toluene (1:1, 5 mL) was treated with N,N-dimethylformamide (2 drops) at 25° C. The reaction mixture was stirred at 25° C. for 2 h. The solution was concentrated in vacuo, and the residue was concentrated three times from toluene (5 mL). The residue was suspended in tetrahydrofuran (5 mL) at 0° C. and then treated with a mixture of 5-dimethoxymethyl-pyrazin-2-ylamine (451 mg, 2.67 mmol) and pyridine (0.216 mL, 2.67 mmol) in tetrahydrofuran (5 mL) over 5 min. At this time, the reaction was allowed to warm to 25° C. where it stirred for 18 h. The resulting mixture was partitioned between ethyl acetate (50 mL) and a dilute aqueous ammonium chloride solution (50 mL). The aqueous layer was separated. The organic layer was sequentially washed with water (1×25 mL), a saturated aqueous sodium bicarbonate solution (1×25 mL), water (1×25 mL), an aqueous copper(II) sulfate solution (1×25 mL), and a saturated aqueous sodium chloride solution (1×25 mL). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 2/3 ethyl acetate/hexanes) afforded the 2-(R)-(3-chloro-4-methanesulfonylphenyl)-3-cyclopentyl-N-(5-dimethoxymethylpyrazin-2-yl)-propionamide (890 mg, 69%) as a pale yellow foam: (ES)+-HRMS m/e calcd for C22H28ClN3O5S (M+H)+ 424.0729, found 424.0733.

후처리

  1. concentrationThe solution was concentrated in vacuo
  2. concentrationthe residue was concentrated three times from toluene (5 mL)
  3. customwas suspended in tetrahydrofuran (5 mL) at 0° C.
  4. temperatureto warm to 25° C. where it
  5. stirringstirred for 18 h
  6. customThe resulting mixture was partitioned between ethyl acetate (50 mL)
  7. customThe aqueous layer was separated
  8. washThe organic layer was sequentially washed with water (1×25 mL)
  9. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8dc42d8e74e44cd483ac7825d4dcbe60
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07132425B2

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